Microbial genetic composition tunes host longevity

Bing Han, Chih-Chun J. Lin, Isaiah A.A. Neve, Jessica N. Sowa and Meng C. Wang et al.

Cell 2017; 169, 1249–1262

Speaker: Chia-Yu Kang (康家瑜)                                    Time: 13:00~14:00, Nov. 22, 2017

Commentator: Dr. Jenn-Wei Chen (陳振暐老師)           Place: Room 601

Abstract

  Homeostasis of diverse gut microbiota can impact human metabolism and immune function; indeed, previous research has shown the ageing process may be associated with gut microbiota in elderly people¹. However, it is still unknown whether targeting gut microbes can be effective in promoting healthy aging. In order to investigate whether the genetic composition of the micrbiome could be an important role of longevity, the authors screened 3983 Escherichia coli mutants in the host Caenorhabditis elegans. They discovered that 29 bacterial genes, when deleted, increased the host longevity. Besides, 12 of bacterial mutants significantly delayed the age-related progression of tumor growth and accumulation of amyloid-beta, a characteristic of neurodegenerative disease in humans. Interestingly, they also found that several genes promoted longevity through increased the polysaccharide colanic acid (CA), an exopolysaccharide secreted by many enterobacterial species that regulates mitochondrial dynamics and unfolded protein response (UPR^mt) in the host^2,3. Purified CA supplementation prolonged the lifespan of C. elegans to induce mitochondria fission via ATFS-1, a host UPR^mt-responsive transcription factor. Also, this mechanism showed the similar effects in wild-type Drosophila melanogaster. In summary, the studies reveal the significance of microbial genetic variations in modulating host longevity. Moreover, the identified molecular targets provide a roadmap in developing pro-longevity microbes and bacterial metabolite acting on host mitochondria to promote longevity.

References

1          Kong, F. et al. Gut microbiota signatures of longevity. Curr Biol 26, R832-R833, doi:10.1016/j.cub.2016.08.015 (2016).

2          Grant, W. D., Sutherland, I. W. & Wilkinson, J. F. Exopolysaccharide colanic acid and its occurrence in the Enterobacteriaceae. J Bacteriol 100, 1187-1193 (1969).

3          Chen, J., Lee, S. M. & Mao, Y. Protective effect of exopolysaccharide colanic acid of Escherichia coli O157:H7 to osmotic and oxidative stress. Int J Food Microbiol 93, 281-286, doi:10.1016/j.ijfoodmicro.2003.12.004 (2004).